Dry eye disease (DED) is a common, age-related ocular condition that in its mildest forms causes bothersome symptoms of ocular discomfort, fatigue, and visual disturbance that interfere with quality of life and in its more severe forms causes chronic pain and fluctuating vision. Current treatments for DED are inadequate and expensive. Both clinical and pre-clinical research has demonstrated that inflammation of the ocular surface is associated with DED, regardless of the cause of DED. Both physicians and patients are increasingly turning to natural treatments for relief, specifically ?3 polyunsaturated fatty acids (PUFAs). ?3 PUFAs have anti-inflammatory actions, which have led clinicians and patients to assume that this dietary supplementation helps dry eye sufferers. ?3 supplements are often recommended by clinicians and widely promoted in the lay press despite only very limited data on the efficacy of ?3 for the treatment of DED. The Dry Eye Evaluation and Management (DREAM) addresses the scientific gap in knowledge of dry eye treatment, specifically ?3, and expands knowledge of the behavior over time of DED signs, symptoms, and inflammatory biomarkers. Completion of a sequential set of two double-masked randomized clinical trials will provide the highest level of evidence on the efficacy of ?3 for DED and information on the long-term effects of supplementation. In addition, the planned longitudinal assessment will provide the first comprehensive description of the changes in characteristics of DED over 1 year in untreated eyes (only artificial tears). Data from the clinical trials and the longitudinal assessment will allow evaluation of inflammatory biomarkers and signs that may be used in tracking and predicting change in disease status, and may improve our understanding of the pathogenesis of DED. The results of these activities will form an evidence base for future research in the area of DED and ocular surface abnormalities. If ?3 proves to be efficacious it would provide an alternative to other treatments, including pharmaceuticals, thereby decreasing health expenditures for medications and professional care, and improving productivity and quality of life in those with DED. Results of DREAM will have immediate clinical implications.